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Relative Resistance of Slow-Growing Strains of Toxoplasma Gondii to Pyrimethamine (Daraprim)
HERBERT E. KAUFMAN, M.D.;
JACK REMINGTON, M.D.;
MARJORIE L. MELTON, B.A.;
LEON JACOBS, Ph.D.
AMA Arch Ophthalmol. 1959;62(4):611-615.
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Both Eyles1 and Summers,2 working independently, discovered that pyrimethamine (Daraprim) cured acute experimental toxoplasmosis in mice. A subsequent study of the action of pyrimethamine and sulfadiazine3 revealed that in mice infected with moderate inocula of RH-strain organisms (less than 20,000 parasites) the drugs acted synergistically and were toxoplasmicidal, when given early enough in the course of infection. When larger inocula were used, however, the same combination of pyrimethamine and sulfadiazine, at the highest doses tolerated, did not kill all the parasites, although the mice survived. Similarly, Cook and Jacobs4 noted that, while pyrimethamine was generally toxoplasmicidal at a concentration of 0.3 mg. % when tested against RH-strain organisms in monkey-kidney tissue cultures, occasionally some organisms remained alive. They reported also that nonproliferating parasites, suspended in tissue culture medium without cells, were apparently unaffected by the drug. Cook then developed a strain of RH toxoplasmas resistant to pyrimethamine
. . . [Full Text PDF of this Article]
Author Affiliations
Boston; Bethesda, Md.
From the Ophthalmology Branch, National Institue of Neurological Diseases and Blindness (Dr. Kaufman), and the Laboratory of Tropical Diseases, National Institute of Allergy and Infectious Diseases (Drs. Remington and Jacobs, and Miss Melton), National Institutes of Health, Public Health Service, U. S. Department of Health, Education, and Welfare.
Footnotes
Submitted for publication April 10, 1959.
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